The evidence to support recommendations that elevated intakes of ascorbic acid (AA) are beneficial with surgery is inadequate and unconvincing. Although decreased plasma and leukocyte AA levels without a concomitant increase in urine excretion of AA are observed post-surgery, a meaningful interpretation of the significance of these observations is not possible with our current knowledge of AA metabolism. There is no basic understanding of AA metabolism following surgery, nor of the influence of AA status on recovery from surgery. The physiological response to surgery is characterized by an elevation in the circulating level of many hormones. Activation of the adrenocortical axis is thought to be particularly related to AA metabolism. Although there is no evidence that directly links the effects of ACTH on AA metabolism with the effects of surgery on ACTH metabolism, it is hypothesized that the effects of surgery are mediated through the elevation in ACTH. The overall objectives of these investigations are to examine the hypotheses that surgery alters AA metabolism and this influence is dependent on the level of AA nutriture, and that ACTH mediates the changes in AA observed with surgery. The specific aims are to: (1) develop the guinea pig surgery model and quantify the plasma cortisol response at varying levels of AA intake, (2) develop the long-term ACTH stimulated animal model, with plasma cortisol level elevated to the same magnitude as observed with surgery, and (3) characterize the kinetics of AA in these two animal models. Studies to determine the half-life of AA, calculated from the plasma AA specific activity curve, tissue concentration, and uptake and retention of the vitamin over time after an i.p. injection of [1-14C]-AA, will be conducted. Evaluation of these AA parameters in the surgery model, with animals ingesting varying levels of AA, will document if surgery alters AA kinetics and if this alteration is dependent on AA status. Comparison of the effects of surgery with the effects of ACTH treatment, on AA kinetics, will clarify the relationship between these physiological states, and will greatly enhance our understanding of the role of ACTH in directing the metabolic fate of AA. The proposed studies will provide the foundation for determining the role of AA in recovery from surgery, and for future studies to elucidate the physiological significance of the observed changes.